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A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis (ASSET)

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ClinicalTrials.gov Identifier: NCT02161406
Recruitment Status : Active, not recruiting
First Posted : June 11, 2014
Last Update Posted : March 8, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Dinesh Khanna, MD, MS, University of Michigan

Brief Summary:
The study hypothesis is that SC abatacept is safe and shows evidence of efficacy (improvement in modified Rodnan score [mRSS]) in patients with diffuse cutaneous systemic sclerosis (dcScc) compared to matching placebo.

Condition or disease Intervention/treatment Phase
Diffuse Cutaneous Systemic Sclerosis Drug: Abatacept Drug: Placebo Phase 2

Detailed Description:
This study is a randomized placebo-controlled double-blind phase 2 trial of patients with dcSSc. Eligible participants will be randomized in a 1:1 ratio to either 125 mg SC abatacept or matching placebo, stratified by duration of dcSSc disease duration (<18 months vs >18 to </=36 months). Study participants will be treated for 12 months on double-blind study medication, followed by an additional 24 weeks of open-label SC abatacept therapy. 86 patients will be randomized in approximately 35 centers in the US, Canada and Europe, with the goal of analyzing 74 participants. The investigators study will test whether abatacept is statistically superior to placebo in reducing the MRSS at month 12 and explore the ability of abatacept to prevent or reverse progression in patients with early disease duration and lower MRSS scores, and reverse established disease in patients with longer disease duration and higher MRSS scores.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.
Study Start Date : September 2014
Estimated Primary Completion Date : September 28, 2018
Estimated Study Completion Date : September 28, 2018


Arm Intervention/treatment
Active Comparator: Abatacept
125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension
Drug: Abatacept
Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks
Other Name: Orencia

Placebo Comparator: Placebo
125mg Placebo
Drug: Placebo
125 mg of Placebo




Primary Outcome Measures :
  1. Incidence of adverse events (AEs) and Serious AEs (SAEs) [ Time Frame: 52 weeks ]
    Safety is measured using AEs, including clinical significant changes in vital signs, laboratory test abnormalities and clinical tolerability of abatacept, and using serious AEs

  2. Change from baseline in the modified Rodnan skin score (mRSS) to month 12 [ Time Frame: Baseline and 52 weeks ]
    The efficacy of treatment on skin fibrosis will be measured by changes from baseline to month 12 in mRSS, a measure of skin thickness.


Secondary Outcome Measures :
  1. Positive or negative change on 28- tender/swollen joint counts [ Time Frame: Baseline and 52 weeks ]
  2. Change in subject reported outcomes [ Time Frame: Baseline and 52 weeks ]
    Quality of life questionaires will be used to capture this data.

  3. Change in % predicted FVC [ Time Frame: Baseline and 52 weeks ]

Other Outcome Measures:
  1. Development of new/worsening cardiac involvement [ Time Frame: Between baseline and 1 year ]
  2. Change in blood and skin biomarkers [ Time Frame: Between baseline and 6 months ]
  3. Digital ulcer net burden at 12 months [ Time Frame: 1 year ]
  4. New Renal Crisis [ Time Frame: 1 year ]
  5. Change from baseline in BMI [ Time Frame: 1 year ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
  2. Diffuse Systemic Sclerosis (dcSSc) as defined by LeRoy and Medsger
  3. Disease duration of ≤ 36 months (defined as time from the first non−Raynaud phenomenon manifestation)
  4. For disease duration of ≤ 18 months: ≥ 10 and ≤ 35 mRSS units at the screening visit
  5. For disease duration of >18-36 months: ≥ 15 and ≤ 45 mRSS units at the screening visit and one of the following:

    • Increase ≥ 3 in mRSS units compared with the last visit within previous 1-6 months
    • Involvement of one new body area with ≥ 2 mRSS units compared with the last visit within the previous 1-6 months
    • Involvement of two new body areas with ≥ 1 mRSS units compared with the last visit within the previous 1-6 months
    • Presence of 1 or more Tendon Friction Rub
  6. Age ≥ 18 years at the screening visit
  7. If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits
  8. Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for

    • 2 weeks prior to and including the baseline visit.
  9. ACE inhibitors, calcium-channel blockers, proton-pump inhibitors, and/or oral vasodilators are permitted if the patient is on a stable dose for ≥ 2 weeks prior to and including the baseline visit.

Exclusion Criteria:

  1. Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
  2. Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
  3. Major surgery (including joint surgery) within 8 weeks prior to screening visit
  4. Infected ulcer prior to randomization
  5. Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit
  6. Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and ABA
  7. Anti-CD20, and cyclophosphamide within 12 months prior to baseline visit.
  8. Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit
  9. Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation
  10. Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline visit
  11. Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within≤ 4 weeks prior to the baseline visit
  12. Treatment with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit
  13. Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit
  14. Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH. It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers.
  15. Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).
  16. Positive for hepatitis B surface antigen prior to the baseline visit
  17. Positive for hepatitis C antigen, if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay prior to baseline visit
  18. Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).
  19. Any of the following at the screening visit: Hemoglobin <8.5 g/dL; WBC < 3,000/mm3 (<3 x 109/L); platelets < 100,000/mm3 (<3 x 109/L); serum creatinine > 2 x ULN; serum ALT or AST > 2 x ULN
  20. Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen
  21. Patients with a history of anaphylaxis to abatacept

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02161406


  Hide Study Locations
Locations
United States, California
Arthritis Associates of Southern California
Los Angeles, California, United States, 90045
University of California- Los Angeles
Los Angeles, California, United States, 90095
Stanford University
Redwood City, California, United States, 94063
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20009
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Harvard Mass General
Boston, Massachusetts, United States, 02116
Boston University
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
Rutgers University Clinical Research Center
New Brunswick, New Jersey, United States, 08831
United States, New York
Steffens Scleroderma Center
Albany, New York, United States, 12203
NorthWell Health
Great Neck, New York, United States, 11021
Hospital for Special Surgery
New York, New York, United States, 10021
Columbia University
New York, New York, United States, 10032
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University Medical Center
Columbus, Ohio, United States, 43221
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
University of Texas Health Center at Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Swedish Health Services
Seattle, Washington, United States, 98122
Canada, Ontario
St. Joseph Health Care London
London, Ontario, Canada, N6A4V2
Mount Sinai Hospital
Toronto, Ontario, Canada, M5T 3L9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
United Kingdom
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Dinesh Khanna, MD, MS
Bristol-Myers Squibb
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Dinesh Khanna, MD, MS University of Michigan

Additional Information:
Responsible Party: Dinesh Khanna, MD, MS, Associate Professor of Rheumatology/ Internal Medicine, University of Michigan
ClinicalTrials.gov Identifier: NCT02161406     History of Changes
Other Study ID Numbers: IM101-344
1UM1AI110557 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2014    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dinesh Khanna, MD, MS, University of Michigan:
Scleroderma

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents